Flavored e-cigarette use in adolescents: Behavioral, cellular, and epigenetic mechanisms

青少年使用调味电子烟：行为、细胞和表观遗传机制

• 批准号: 9521691
• 负责人: Mariella De Biasi
• 金额: $ 44.16万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9521691
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Affect; Age; Aldehydes; Area; Behavioral; Beverages; Biochemical; Brain; Candy; Centers for Disease Control and Prevention (U.S.); Cessation of life; ChIP-seq; Chemical Actions; Chemicals; Cigarette; Clinical Research; Complement; Complex; Consumption; Cues; Dependence; Development; Devices; Disease; Dopamine; Dopaminergic Cell; Dose; Electronic cigarette; Electrophysiology (science); Epigenetic Process; Ethanol; Exclusion; Experimental Models; Exposure to; Familiarity; Food; Fostering; Fruit; Genes; Goals; High School Student; Histones; Human; Inhalation; Injections; Investigation; Lead; Life; Liquid substance; Mass Spectrum Analysis; Measures; Menthol; Modeling; Modification; Molecular; Monitor; Mus; Neurons; Nicotine; Nicotine Dependence; Oral; Pathway interactions; Periodicity; Pharmaceutical Preparations; Pharmacologic Actions; Post-Translational Protein Processing; Predisposition; Property; Rewards; Risk; Self Administration; Sensory; Series; Stimulus; Sucrose; System; Techniques; Teenagers; Testing; Tobacco; Weather; addiction; awake; behavioral study; dopaminergic neuron; electronic cigarette use; experience; experimental study; genetic approach; histone modification; in vivo; interest; junior high school; neuroadaptation; nicotine abuse; nicotine exposure; nicotine seeking behavior; nicotine use; nicotine vapor; pre-clinical; preclinical study; preference; response; reward circuitry; sensory input; soft drink; transcriptome; vaping; vapor; young adult

E-cigarettes are increasingly used by teenagers, who are particularly vulnerable to the addictive properties of nicotine. With the exclusion of menthol, the use of flavor additives has been banned from traditional cigarettes, while e-cigarettes are marketed in over 7,000 different flavors. Many of those flavors are found in candy and popular soft drinks and, because they are familiar, make e-cigarettes more appealing to adolescents. We hypothesize that flavorants enhance nicotine reward through sensory and/or natural reward mechanisms. As a consequence, flavored e-cigarettes may promote nicotine experimentation, dependence, and eventually, the use of regular cigarettes. Understanding how flavors influence e-cigarette use is important for the implementation of regulatory rules that can reduce potential disease and death deriving from the consumption of this increasingly popular tobacco product. The goal of this application is to compare the rewarding and reinforcing properties of flavored vs. non-flavored e-cigarettes in adolescent mice. Our hypothesis is that flavored e-cigarettes are more rewarding than non-flavored e-cigarettes, and that flavor additives promote and sustain nicotine seeking in adolescents. The first goal is to determine whether sweet flavorants enhance adolescent nicotine reward and promote nicotine self-administration. The second goal is to investigate the possibility that a learned flavor preference, which models exposure to sweetened food and beverages at a young age, will further enhance flavor-induced nicotine reward and self-administration. Finally, we will determine whether exposure to flavored e-cigarettes at young age increases the risk of nicotine abuse in adulthood. These behavioral experiments will be complemented by a series of molecular investigations. First, we will employ in vivo tetrode recording to measure changes in dopamine neuron firing during exposure to flavored and non-flavored e-cig nicotine vapor. Second, we will utilize in vivo voltammetry techniques to quantitatively measure dopamine release in the NAc in response to inhalation of flavored vs.unflavored e-cigarette vapors. Third, we will utilize state-of-the art approaches to determine whether e-cigarette nicotine vapor changes the epigenetic landscape of reward- associated brain areas, and weather fruit flavorants have additive or synergistic effects.

青少年越来越多地使用电子烟，他们特别容易受到上瘾的人的影响 尼古丁的特性。随着薄荷醇的排除，香料添加剂的使用已被禁止 传统香烟，而电子烟有超过7000种不同的口味。其中很多都是 香料存在于糖果和受欢迎的软饮料中，因为人们熟悉它们，所以可以制造电子烟。 对青少年更有吸引力。我们假设调味剂通过 感官和/或自然奖励机制。因此，调味电子烟可能会促进 尼古丁实验、依赖，并最终使用普通香烟。理解 口味如何影响电子烟的使用对于实施监管规则非常重要，这些规则可以 减少因食用这种日益流行的烟草而导致的潜在疾病和死亡 产品。 此应用程序的目标是比较调味品的奖励和增强特性 对青春期小鼠的电子烟与非调味电子烟的比较。我们的假设是加味电子烟比普通电子烟 比无香料的电子烟更有价值，而且香料添加剂促进和维持尼古丁 青少年中的寻求者。第一个目标是确定甜味剂是否对青少年有促进作用 尼古丁奖励并促进尼古丁自我管理。第二个目标是调查 一种习得的味道偏好的可能性，它模拟了对含糖食物和饮料的接触 在年轻的时候，会进一步增强香精诱导的尼古丁奖励和自我给药。最后，我们 将确定年轻时接触调味电子烟是否会增加尼古丁的风险 成年后的虐待行为。这些行为实验将得到一系列分子的补充 调查。首先，我们将使用活体四极管记录来测量多巴胺神经元的变化 在接触有味和非有味的电子烟尼古丁蒸气时开枪。第二，我们将利用体内 伏安法定量测定NAC中多巴胺释放量 吸入有香料的电子烟蒸气与无香料的电子烟蒸气。第三，我们将利用最先进的方法 为了确定电子烟尼古丁蒸气是否改变了奖励的表观遗传格局-- 相关的大脑区域和天气水果调味剂具有相加或协同作用。